Single-cell multiomics defines tolerogenic extrathymic Aire-expressing populations with unique homology to thymic epithelium

• DOI: 10.1126/sciimmunol.abl5053
• Publication Date: 2021-11-12T18:58:11Z
• Authors: Jiaxi Wang; Caleb A. Lareau; Jhoanne L. Bautista; Alexander R. Gupta; Katalin Sandor; Joe Germino; Yajie Yin; Matthew P. Arvedson; Gabriella C. Reeder; Nathan T. Cramer; Fang Xie; Vasilis Ntranos; Ansuman T. Satpathy; Mark S. Anderson; James M. Gardner
• Keywords: Homology; Fate mapping; Lymphopoiesis

The autoimmune regulator (Aire), a well-defined transcriptional in the thymus, is also found extrathymic Aire-expressing cells (eTACs) secondary lymphoid organs. eTACs are hematopoietic antigen-presenting and inducers of immune tolerance, but their precise identity has remained unclear. Here, we use single-cell multiomics, transgenic murine models, functional approaches to define at transcriptional, genomic, proteomic level. We find that consist two similar cell types: CCR7+ migratory dendritic (AmDCs) an Airehi population coexpressing Aire retinoic acid receptor–related orphan receptor γt (RORγt) term Janus (JCs). Both JCs AmDCs have highest genomic homology cells. eTACs, particularly JCs, highly accessible chromatin broad gene expression, including range tissue-specific antigens, as well remarkable medullary thymic epithelium RANK-dependent expression. Transgenic self-antigen expression by sufficient induce negative selection prevent diabetes. This symmetry between (both AmDCs) epithelium—the other principal key central tolerance—identifies core program may influence self-representation tolerance across spectrum development.